Abstract: A variety of small molecule, guanidine-containing molecules capable of acting as MC4-R agonists are provided. The compounds are useful in treating MC4-R mediated diseases when administered to subjects. The compounds have the formula IA and IB.

Abstract: The invention provides a method of treating or preventing a pathologic state in a mammal. The method comprises administering to the mammal a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system. The promoter of T-cell expansion and inducer of CD40 stimulation are administered in synergistically effective amounts to treat or prevent the pathologic state in the mammal. The invention also provides a method of assessing the effectiveness of treatment of a pathologic state in a mammal, wherein the mammal has been administered a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system.

Abstract: Organic compounds having the structural formula I are provided where the variables have the values described herein and R1 and R2 join together to form a 6 membered substituted or unsubstituted ring including at least one O, N, or S atom, and Z is an O, S, NH or NR group. Pharmaceutical formulations include the organic compound or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

Abstract: A patient suffering from an endobronchial infection is treated by administering to the patient for inhalation a dose of less than about 4.0 ml of a nebulized aerosol formulation comprising from about 60 to about 200 mg/ml of an aminoglycoside antibiotic, such as tobramycin, in a physiologically acceptable carrier in a time period of less than about 10 minutes. Unit dose devices for storage and delivery of the aminoglycoside antibiotic formulations are also provided.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Heteroaryl-fused pyrimidinyl compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the heteroaryl-fused pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the heteroaryl-fused pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.

Abstract: Heteroaryl-fused pyrimidinyl compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the heteroaryl-fused pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the heteroaryl-fused pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.

Abstract: Methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40 expressing cells, such as B cells.

Abstract: The present invention is directed to the purification and commercialization of therapeutic polypeptides that have. In one aspect of the invention, a method of purifying Interferon ?-1b using size exclusion chromatography is provided. In another aspect of the invention, a method of purifying a polypeptide using size chromatography is provided. A third aspect provides a method of commercializing a polypeptide.

Abstract: The present invention is a novel nucleic acid sequence which hybridizes to SEQ ID NO:6 or fragments thereof under stringent conditions, or fragments thereof. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecules, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.

Abstract: Pyridin[1,2-a]pyrimidinyl compounds, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the pyridino[1,2-a]pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent. Methods of using the pyridino[1,2-a]pyrimidinyl compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases.

Abstract: New substituted benz-azole compounds, compositions and methods of inhibition of Raf kinase activity in a human or animal subject are provided. The new compounds compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.

Abstract: The present invention relates to novel sequences for use in detection, diagnosis and treatment of diseases, including cancer. The invention provides novel splice forms of human DKKL 1 gene. The present invention provides methods of using polynucleotides having the novel splice variants of the human DKKL 1 sequences, their corresponding gene products and antibodies specific for the gene products in the detection, diagnosis, prevention and/or treatment of associated cancers.

Abstract: The invention provides the three-dimensional structure of a construct of human glycogen synthase kinase 3 (GSK3); crystals of a construct of human glycogen synthase kinase 3-? (GSK3-?) containing the protein's catalytic kinase domain; a method for crystallizing the protein construct to provide a GSK3 crystal sufficient for structure determination; and a method for using the GSK3 construct's three-dimensional structure for the identification of possible therapeutic compounds in the treatment of various disease conditions mediated by GSK3 activity.

Abstract: Inhibitors of human Sos1, including antisense oligonucleotides, methods, and compositions specific for human Sos1, are provided. Methods of using the compositions for modulating Sos1 expression and for regulating cell growth, particularly tumor cell growth, are also provided.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The invention provides a method of activating hepatitis C virus (HCV)-specific T cells, including CD4+ and CD8+ T cells. HCV-specific T cells are activated using fusion proteins comprising HCV NS3, NS4, NS5a, and NS5b polypeptides, polynucleotides encoding such fusion proteins, or polypeptide or polynucleotide compositions containing the individual components of these fusions. The method can be used in model systems to develop HCV-specific immunogenic compositions, as well as to immunize a mammal against HCV.

Abstract: Gene sequences as shown in SEQ ID NO:1-18 have been discovered and isolated, and found to be significantly associated with metastatic spread of breast and colon cancer cells to other organs. Methods are provided for determining the risk of metastasis of a breast or colon tumor, which involve determining whether a tissue sample from a tumor expresses a polypeptide encoded by a gene as shown in SEQ ID NOS:1-18, or a substantial portion thereof. One of the gene sequences encodes a novel aspartyl protease termed CSP56, which can be used to provide reagents and methods for determining which tumors are likely to metastasize and for suppressing metastases of these tumors. Clinicians can use this information to predict which tumors will metastasize to other organs and to provide relevant therapies to appropriate patients.

Abstract: The invention provides polynucleotides encoding Notch receptor ligands, encoded polypeptides, and antibodies specific to the polypeptides. Also provided are methods and compositions for enhancing or inhibiting angiogenesis as well as modulating immune responses.

Abstract: The invention provides a method of treating or preventing a pathologic state in a mammal. The method comprises administering to the mammal a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system. The promoter of T-cell expansion and inducer of CD40 stimulation are administered in synergistically effective amounts to treat or prevent the pathologic state in the mammal. The invention also provides a method of assessing the effectiveness of treatment of a pathologic state in a mammal, wherein the mammal has been administered a promoter of T-cell expansion and an inducer of CD40 stimulation, wherein CD40 is stimulated on cells of the immune system.